The ASPIRE Path in Molecular Medicine

I am a graduate student in Dr. David Wasserman’s laboratory. Research in the Wasserman laboratory is focused on understanding the mechanisms that drive obesity-induced insulin resistance, the precursor state to Type II diabetes. Insulin resistance is characterized by impaired insulin-stimulated glucose uptake into skeletal muscle, the primary site for insulin-stimulated glucose disposal. Despite decades of research, the underlying mechanisms by which skeletal muscle becomes insulin resistant remain unclear. In my thesis work, I am exploring the idea that impaired skeletal muscle insulin action is a manifestation of reduced vascular insulin delivery. Before insulin can stimulate muscle glucose uptake, it must first move from the plasma, across the continuous endothelium, and into the interstitial fluid bathing myocytes. Little is known about transendothelial insulin efflux because there are currently no methods to measure it. Therefore, I have developed an in vivo imaging technique whereby I can measure the rate at which a fluorescent insulin probe moves from the capillaries to the interstitial space in mice. I will use this technique to 1) determine whether insulin transits the endothelium by diffusion or receptor-mediated transport and 2) determine how insulin efflux is affected in the setting of obesity.

My clinical mentor is Dr. John Cleator, an interventional cardiologist in the Division of Cardiovascular Medicine. Dr. Cleator’s research and clinical interests are in the role of thrombin receptors in regulating coronary blood flow and the response to percutaneous coronary intervention. It will be greatly beneficial to get a clinical perspective on human cardiovascular physiology and atherosclerosis given that my thesis work involves assessing vascular function in mice. Furthermore, Dr. Cleator will help me explore the possibility of moving my in vivo insulin imaging technique from mice to humans.